Instability Signals and New Opportunities in the Rare Cardiovascular Market (ATTR-CM)

The burgeoning field of transthyretin amyloid cardiomyopathy (ATTR-CM)—once projected to become a $20 billion market—may have just revealed the first indication of a slowdown, raising concerns about the market expansion potential for newer entrants.

Market Leader’s Sales Performance:

In the third quarter, Pfizer reported a 1% year-over-year sales decline for its tafamidis products in the U.S., which also represented a 4% sequential drop from the previous quarter. Though the dip was small, it warrants scrutiny, particularly as it occurs less than a year after the launch of the rival drug Attruby (BridgeBio) and two full quarters after Amvuttra(Alnylam) entered the market.

Market analysts suggest that the moderation in the category’s previously “torrid pace of growth” is a cause for concern, as considerable interest was built on the assumption that the market was large enough for multiple players to thrive together.

Response from Newer Entrants:

The new entrants remain confident that underlying patient demand is still growing, even if Pfizer’s dollar revenue was impacted by pricing dynamics (such as Inflation Reduction Act rebates and payer discounts):

• BridgeBio: The CEO acknowledged that the speed of expansion (the “growth of the growth”) appears to be flattening but affirmed that the overall prescription growth rate “continues to be profound,” with the overall magnitude of new patients increasing at an unprecedented level.

• Alnylam: Reported an approximate doubling in patient demand for Amvuttra (the injectable gene silencer) in the third quarter versus the second quarter.

Differentiation Strategy and the Generic Future:

Companies are focusing on differentiating their products and preparing for the loss of patent protection for Pfizer’s tafamidis in the U.S. in 2028:

1. Attruby (BridgeBio): The focus is on differentiating the drug as a best-in-class, first-line stabilizer with greater potency than Pfizer’s product. Despite its twice-daily dosing schedule (vs. once daily for the competitor), BridgeBio argues that the differential efficacy (maintaining TTR stabilization above 90%) is a higher priority in this severe, life-threatening condition.

2. Amvuttra (Alnylam): The company expects to benefit from the advent of generic tafamidis. Alnylam is banking on a combination therapy approach (Amvuttra plus generic tafamidis) gaining broader uptake once the financial burden is relieved, allowing them to benefit from patient volume expansion without competing directly for market share.

Market Expansion and Upcoming Competition:

While only about one-fifth of the estimated 250,000 to 300,000 ATTR-CM/HFpEF patients in the U.S. are properly diagnosed, experts believe that the entry of multiple players will improve awareness and diagnosis rates.

• Potential Competitor: A fourth player, Wainua (from AstraZeneca and Ionis), is expected to read out Phase 3 trial data in the second half of 2026. Given AstraZeneca’s strong cardiovascular franchise, its potential participation is viewed as a factor that could reaccelerate overall market growth.

• Research Challenge: Conversely, the push for earlier and milder disease diagnosis could pose a challenge for newer generation drug candidates (like Alnylam’s nucresiran), making it more difficult to demonstrate a treatment effect in future clinical trials.

Analysts currently show wide divergence in market projections, with estimated global total ATTR drug sales for 2028 ranging from $15.3 billion to $16.7 billion.

Soucre: https://www.fiercepharma.com/pharma/pfizer-reported-attr-sales-decline-us-should-alnylam-bridgebio-worry